Oncotarget

Research Papers: Gerotarget (Focus on Aging):

Methylomic predictors demonstrate the role of NF-κB in old-age mortality and are unrelated to the aging-associated epigenetic drift

Juulia Jylhävä _, Laura Kananen, Jani Raitanen, Saara Marttila, Tapio Nevalainen, Antti Hervonen, Marja Jylhä and Mikko Hurme

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Oncotarget. 2016; 7:19228-19241. https://doi.org/10.18632/oncotarget.8278

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Abstract

Juulia Jylhävä1,2, Laura Kananen1,2, Jani Raitanen3,4, Saara Marttila1,2, Tapio Nevalainen1,2, Antti Hervonen2,3, Marja Jylhä2,3 and Mikko Hurme1,2,5

1 Department of Microbiology and Immunology, School of Medicine, University of Tampere, Tampere, Finland

2 Gerontology Research Center, University of Tampere, Tampere, Finland

3 School of Health Sciences, University of Tampere, Tampere, Finland

4 UKK Institute for Health Promotion Research, Tampere, Finland

5 Fimlab Laboratories, Tampere, Finland

Correspondence to:

Juulia Jylhävä, email:

Keywords: methylation, mortality, aging, longevity, Cox model, Gerotarget

Received: November 06, 2015 Accepted: March 10, 2016 Published: March 22, 2016

Abstract

Changes in the DNA methylation (DNAm) landscape have been implicated in aging and cellular senescence. To unravel the role of specific DNAm patterns in late-life survival, we performed genome-wide methylation profiling in nonagenarians (n=111) and determined the performance of the methylomic predictors and conventional risk markers in a longitudinal setting. The survival model containing only the methylomic markers was superior in terms of predictive accuracy compared with the model containing only the conventional predictors or the model containing conventional predictors combined with the methylomic markers. At the 2.55-year follow-up, we identified 19 mortality-associated (false-discovery rate <0.5) CpG sites that mapped to genes functionally clustering around the nuclear factor kappa B (NF-κB) complex. Interestingly, none of the mortality-associated CpG sites overlapped with the established aging-associated DNAm sites. Our results are in line with previous findings on the role of NF-κB in controlling animal life spans and demonstrate the role of this complex in human longevity.


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